System and method for selecting differentially dependent genes from gene expression data

Abstract

Dependence between expression levels of different genes is identified through a multivariate method of statistical analysis of single color microarray gene expression data. An algorithm is applied to gene data to identify those genes that are likely to change their relationship with all other genes, and select such genes for further investigation. If genes change their relationship to other genes from phenotype to phenotype, they are treated as likely to change their relationship with one another.

1 . A method for establishing investigative priorities for genes, the method comprising: 
 (a) drawing subsamples of vectors from first and second groups of vectors representing expression levels of the genes;    (b) computing a correlation vector of the subsampled vectors in the first group,    (c) computing a correlation vector of the subsampled vectors in the second group,    (d) determining values representing the correlation vectors,    (e) applying a statistical test to the values representing the correlation vectors to obtain p-values;    (f) analyzing the p-values to identify those genes that have a likelihood of changing their relationship with other genes in the sample that exceeds a selected threshold; and    (g) generating an output of results identifying one or more genes that may change their relationship with other genes.    
   
   
       2 . The method of  claim 1 , further comprising using the output in establishing investigative priorities for gene evaluation.  
   
   
       3 . The method of  claim 1 , wherein steps (a) through (c) are performed k times to obtain k correlation vectors, where k>1 is a number of the subsamples.  
   
   
       4 . The method of  claim 3 , wherein said k correlation vectors are obtained three times.  
   
   
       5 . The method of  claim 4 , wherein m unadjusted p-values are obtained, where m>1 is a number of the genes.  
   
   
       6 . The method of  claim 1 , wherein the statistical test is a univariate test.  
   
   
       7 . The method of  claim 1 , wherein step (a) comprises drawing subsamples for a plurality of different phenotypes.  
   
   
       8 . The method of  claim 7 , wherein step (f) comprises identifying those genes whose relationship with other genes varies according to the plurality of different phenotypes.  
   
   
       9 . A device for establishing investigative priorities for genes, the device comprising: 
 an input for receiving first and second groups of vectors representing expression levels of the genes;    a processor, in communication with the input, for:    (a) drawing subsamples of the vectors from the first and second groups of vectors representing the expression levels of the genes;    (b) computing a correlation vector of the subsampled vectors in the first group,    (c) computing a correlation vector of the subsampled vectors in the second group,    (d) determining values representing the correlation vectors,    (e) applying a statistical test to the values representing the correlation vectors to obtain p-values;    (f) analyzing the p-values to identify those genes that have a likelihood of changing their relationship with other genes in the sample that exceeds a selected threshold;    (g) generating an output of results identifying one or more genes that may change their relationship with other genes; and    an output, in communication with the processor, for outputting the output of results generated by the processor.    
   
   
       10 . The device of  claim 9 , wherein the processor performs steps (a) through (c) k times to obtain k correlation vectors, where k>1 is a number of the subsamples.  
   
   
       11 . The device of  claim 10 , wherein said k correlation vectors are obtained three times.  
   
   
       12 . The device of  claim 11 , wherein m unadjusted p-values are obtained, where m> 1  is a number of the genes.  
   
   
       13 . The device of  claim 9 , wherein the statistical test is a univariate test.  
   
   
       14 . The device of  claim 9 , wherein the processor performs step (a) by drawing subsamples for a plurality of different phenotypes.  
   
   
       15 . The device of  claim 14 , wherein the processor performs step (f) by identifying those genes whose relationship with other genes varies according to the plurality of different phenotypes.  
   
   
       16 . An article of manufacture for establishing investigative priorities for genes, the article of manufacture comprising: 
 a computer-readable storage medium; and    code, stored on the computer-readable storage medium, the code, when executed on a processor, controlling the processor for:    (a) drawing subsamples of vectors from first and second groups of vectors representing expression levels of the genes;    (b) computing a correlation vector of the subsampled vectors in the first group,    (c) computing a correlation vector of the subsampled vectors in the second group,    (d) determining values representing the correlation vectors,    (e) applying a statistical test to the values representing the correlation vectors to obtain p-values;    (f) analyzing the p-values to identify those genes that have a likelihood of changing their relationship with other genes in the sample that exceeds a selected threshold; and    (g) generating an output of results identifying one or more genes that may change their relationship with other genes.    
   
   
       17 . The article of manufacture of  claim 16 , wherein the code comprises code for controlling the processor to perform steps (a) through (c) k times to obtain k correlation vectors, where k>1 is a number of the subsamples.  
   
   
       18 . The article of manufacture of  claim 17 , wherein the code comprises code for controlling the processor to obtain said k correlation vectors three times.  
   
   
       19 . The article of manufacture of  claim 18 , wherein the code comprises code for controlling the processor to obtain m unadjusted p-values, where m>1 is a number of the genes.  
   
   
       20 . The article of manufacture of  claim 16 , wherein the statistical test is a univariate test.  
   
   
       21 . The article of manufacture of  claim 16 , wherein the code comprises code for controlling the processor to perform step (a) by drawing subsamples for a plurality of different phenotypes.  
   
   
       22 . The article of manufacture of  claim 21 , wherein the code comprises code for controlling the processor to perform step (f) by identifying those genes whose relationship with other genes varies according to the plurality of different phenotypes.